Several naturally occurring viral infections of domestic animals are studied to learn more about the unusual host-virus interactions giving rise to diseases that evolve slowly after long incubation periods. Two diseases of greatest concern are scrapie of sheep and goats and Aleutian disease of mink. Scrapie is a degenerative disease of the brain (polioencephalopathy) caused by virus replicating in central nervous tissue. Aleutian disease is mainly a chronic disease of the kidneys that is mediated by deposits of infectious immune complexes in the glomeruli. By use of fairly simple methods of clinical observation, serology, virology, animal inoculation, and anatomic pathology, information is sought on the pathogenesis and natural history of each disease. Such information not only will help define the diseases and the mechanisms that give rise to them, but also will help determine the relation of protracted viral infection to the genesis of chronic disease in man. One such human disease, Creutzfeldt-Jakob disease, is included in the project to determine its possible etiologic relation to scrapie.